Antepsin Suspension

1. Name Of The Medicinal Product

Antepsin 1g/5ml Oral Suspension

2. Qualitative And Quantitative Composition

Each 5 mL dose contains 1 gram sucralfate.

For excipients, see section 6.1

3. Pharmaceutical Form

Oral Suspension

White to off-white viscous suspension with an odour of aniseed/caramel.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of duodenal ulcer, gastric ulcer, chronic gastritis, and the prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients.

4.2 Posology And Method Of Administration

For oral administration.

Duodenal ulcer, gastric ulcer, chronic gastritis:

Adults: The usual dose is 2 grams twice daily to be taken on rising and at bedtime, or 1 gram 4 times a day to be taken 1 hour before meals and at bedtime. Maximum daily dose: 8 grams.

Four to six weeks' treatment is usually needed for ulcer healing, but up to twelve weeks may be necessary in resistant cases.

Antacids may be used as required for relief of pain, but should not be taken half an hour before or after Antepsin.

Children and Elderly: see below

Prophylaxis of gastrointestinal haemorrhage from stress ulceration:

Adults: The usual dose is 1 gram six times a day. A maximum dose of 8 grams daily should not be exceeded. Antacids may be used as required for relief of pain, but should not be taken half an hour before or after Antepsin.

Elderly: There are no special dosage requirements for elderly patients but as with all medicines, the lowest effective dose should be used.

Children: Safety and effectiveness in children has not been established.

4.3 Contraindications

Contraindicated in individuals who are hypersensitive to any of the ingredients of Antepsin.

4.4 Special Warnings And Precautions For Use

The product should only be used with caution in patients with renal dysfunction, due to the possibility of increased aluminium absorption.

In patients with severe renal impairment or on dialysis, Antepsin should be used with extreme caution and only for short-term treatment. The concomitant use of other aluminium containing medications is not recommended in view of the enhanced potential for aluminium absorption and toxicity. Antepsin may also cause allergic reactions (possibly delayed).

Bezoars (an insoluble mass formed with the gastric lumen) have been reported occasionally in patients taking Antepsin Suspension. The majority of these patients had underlying conditions that may predispose to bezoar formation such as delayed gastric emptying, or were receiving concomitant enteral feeding (see under Interactions). Bezoars have been reported after administration of Antepsin Suspension to severely ill patients in ITU, especially in premature infants in whom the use of sucralfate is not recommended.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant administration of Antepsin may reduce the bioavailability of certain drugs including tetracycline, ciprofloxacin, norfloxacin, ketoconazole, digoxin, warfarin, phenytoin, theophylline, thyroxine, quinidine and H₂ antagonists. The bioavailability of these agents may be restored by separating the administration of these agents from Antepsin by two hours. This interaction appears to be non systemic in origin presumably resulting from these agents being bound by Antepsin in the gastrointestinal tract. Because of the potential of Antepsin to alter the absorption of some drugs from the gastrointestinal tract, the separate administration of Antepsin from that of other agents should be considered when alterations in bioavailability are felt to be critical for concomitantly administered drugs.

The administration of Antepsin Suspension and enteral feeds by nasogastric tube should be separated by one hour in patients receiving Antepsin Suspension for the prophylaxis of stress ulceration. In rare cases bezoar formation has been reported when Antepsin and enteral feeds have been given too closely together.

4.6 Pregnancy And Lactation

Pregnancy:

Teratogenicity studies in mice, rats and rabbits at doses up to 50 times the human dose have revealed no evidence of harm to the foetus. Safety in pregnant women has not been established and Antepsin should be used during pregnancy only if clearly needed.

Lactation:

It is not known whether this drug is excreted in human milk. Caution should be exercised when Antepsin is administered to breast-feeding women.

4.7 Effects On Ability To Drive And Use Machines

Do not drive if you feel dizzy or drowsy.

4.8 Undesirable Effects

Adverse reactions to Antepsin in clinical trials were minor and only rarely led to discontinuation of the drug. Adverse events seen during use of Antepsin have included constipation, diarrhoea, nausea, vomiting, gastric discomfort, indigestion, flatulence, dry mouth, rash, back pain, dizziness, headache, vertigo, drowsiness and hypersensitivity reactions including pruritus, oedema, urticaria and shortness of breath.

4.9 Overdose

There is no experience in humans with overdose. Acute oral toxicity studies in animals, however, using doses up to 12 g/kg body weight, could not find a lethal dose. Risks associated with overdose, should, therefore, be minimal.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Alimentary tract and metabolism, ATC code: A02B X02

The action of Antepsin is non-systemic as the drug is only minimally absorbed from the gastro-intestinal tract. The small amounts that are absorbed are excreted primarily in the urine. Antepsin exerts a generalised cytoprotective effect by preventing gastro-intestinal mucosal injury.

Studies in humans and animal models show that Antepsin forms an ulcer adherent complex with the proteinaceous exudate of the ulcer site. This property enables Antepsin to form a protective barrier over the ulcer lesion giving sustained protection against the penetration and action of gastric acid, pepsin and bile.

Studies both in humans and animals demonstrate that Antepsin protects the gastric mucosa against various irritants such as alcohol, acetylsalicyclic acid and sodium taurocholate.

Antepsin also directly inhibits pepsin activity and absorbs bile salts. It has only weak antacid activity. It does not alter gastric emptying time, nor normal digestive function. Antepsin has no demonstrated pharmacological effect on the cardiovascular or central nervous systems.

5.2 Pharmacokinetic Properties

Sucralfate is only minimally absorbed from the gastro-intestinal tract. The small amounts that are absorbed are excreted primarily in the urine. Absorption of aluminium from sucralfate may be increased in patients on dialysis or with renal dysfunction (see also “other special warnings and precautions”).

5.3 Preclinical Safety Data

There was no evidence of carcinogenesis in mice and rats receiving oral sucralfate in dosages of up to 1 g/kg daily (12 times the usual human dosage) for 2 years. In animal studies there was no effect evidence of impaired fertility. The effect of sucralfate on human fertility is not known.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Saccharin sodium

Sodium dihydrogen phosphate dihydrate Ph.Eur.

Purified water

Glycerol

Sodium propyl hydroxybenzoate (E217)

Sodium methyl hydroxybenzoate (E219)

Xanthan gum

Aniseed flavour

Caramel flavour

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Store below 25^oC.

6.5 Nature And Contents Of Container

Glass bottle (pack size 250 mL)

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Chugai Pharma UK Ltd.

Mulliner House

Flanders Road

Turnham Green

London

W4 1NN

UK

8. Marketing Authorisation Number(S)

PL 12185/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

29/09/2005

10. Date Of Revision Of The Text

5 November 2007